Current Concepts and Issues in Blood Management

ABSTRACT

Blood management in orthopedic surgery is no longer an option; it is a requirement. The combination of patient desire to avoid transfusion, increasing evidence of multiple risks, decreasing blood supplies, and increasing costs mandate attention. This article addresses the balance of risk versus benefit in blood transfusion and presents a perioperative plan of blood management for patients undergoing orthopedic surgery.

Surgeons have been bound since the time of the ancients by the code of Hippocrates, which Galen translated to the familiar version, “First, do no harm.” This mandate is the basis for the daily assessment of the balance between risk and benefit in the care of patients. Many surgeons face difficulty in performing to this standard when considering blood transfusion. Much is known about the established risks of blood, but little is known about its proven benefit. Surgical ethicists Sugarman and Harland¹ emphasize the need to go beyond listing available options to patients. They propose that the surgeon understand not only the risks and benefits of blood transfusion and the role of alternatives, but also the patient’s belief system or choice. The need to provide the best possible care for patients while respecting patients’ wishes is underscored by the decreasing supply of blood and its concomitant increasing cost. These factors — the balance of risk versus benefit, patient choice, decreasing supplies, and increasing costs — are reasons to embrace a philosophy of blood management.

Risk Versus Benefit of Allogeneic Blood Transfusion

Table 1 Categories of Risk Associated with Allogeneic Blood Transfusion Transfusion reactions Transfusion-transmitted disease Transfusion-related immunomodulation Transfusion-related acute lung injury Cytokine infusion Release of free hemoglobin Microchimerism

Risks are associated with current allogeneic blood transfusion (Table 1). In some cases, the risk of individual reactions is listed as rare or unknown (Table 2). In most instances, this reflects lack of knowledge regarding true incidence from under-reporting. When a hemovigilance program such as the Serious Hazards of Transfusion program is instituted, the magnitude of this problem can be appreciated. Data collected from 1996 to 2000 reported that 25% of reported hazards were caused by either acute or delayed transfusion reactions.²

Some reactions have the potential to kill patients and some occur more often in surgical patients. These are, consequently, of greater interest to the surgeon. Lethal transfusion reactions include those caused by ABO incompatibility, acute hemolysis and anaphylaxis, and bacterial contamination. Deaths associated with hypotensive platelet reactions and transfusion-related acute lung injury have been reported.³ Linden et al^4,5 has estimated the risk of death from an ABO incompatibility reaction as 1:600,000 transfusions, which is comparable to the risk of getting the human immunodeficiency virus (HIV) from a transfusion. Medical and nursing personnel at the bedside cause the majority of ABO incompatibility complications. Labeling and tracking programs can help decrease the incidence.⁶ However, it remains the surgeon’s responsibility to ensure that procedures are followed to protect patients from unwarranted and preventable deaths caused by using the wrong unit of blood.

Anaphylactic, or ABO incompatibility, reactions occur at the bedside, in the trauma unit, or the operating room. Anaphylactic reactions may be caused by incompatible red blood cells or incompatible platelets.⁷ The classic presentation of this reaction in the unconscious or anesthetized patient is sudden, uncontrollable, and unexplained hemorrhage.⁸ The surgeon must act quickly to stop the transfusion because mortality is related to the amount of blood transfused. Bluemle et al⁹ has reported a 44% mortality rate in patients receiving >1000 mL of incompatible blood. This does not provide a margin of safety while the surgeon contemplates why the patient is bleeding because a transfusion of as little as 30 mL of blood has caused death.¹⁰ Prevention and treatment of these lethal transfusion reactions require diligence in handling blood and swift action in the face of a suspected reaction.

Until recently, there has been no way to determine if a unit of blood has been contaminated.¹¹ In a study, Burstain¹² has shown that using a urine dipstick to test a blood unit for bacteria has a sensitivity and specificity of 100%. It is unknown how commonly this test is used. In most patients, the bacterial load is so overwhelming that septic shock and death rapidly ensue. Relief from bacterial load cannot be found in autologous, predonated blood because this can also be contaminated during handling and storage.¹³

An acute, noncardiogenic pulmonary edema is caused by plasma-borne human leukocyte antigens or granulocyte antigens that combine with lipid inflammatory mediators to produce pulmonary capillary injury.¹⁴ Because the antigens are carried in plasma, transfusion-related acute lung injury can be caused by transfusion of red cells, platelets, or fresh frozen plasma. Whether a unit of blood products produce this reaction cannot be determined. Some believe that blood collected from female, multiparous donors may be more likely to produce transfusion-related acute lung injury because of the high levels of reactivity of the plasma, but this has not been demonstrated conclusively.¹⁵ Recent evidence suggests that donor blood product and recipient factors play a role in this reaction.¹⁶ The incidence of transfusion-related acute lung injury is unknown and no specific treatment exists other than supportive care.¹⁷ Blajchman¹⁸ estimates that 0.04% to 0.16% of transfused patients develop transfusion-related acute lung injury.

Every surgeon is aware of the fact that HIV can be transmitted by blood transfusion and can produce the clinical disease of acquired immuno deficiency syndrome (AIDS). Levels of individual awareness and concern decrease dramatically when the discussion turns to other diseases. Interest and knowledge depend on what was taught during training, individual experience, and practice location. Table 3 lists the agents known to be transfusion-transmissible, clinical relevance, and estimates of risk. The list is not complete and increases each year, as more diseases are proven to be transfusion-transmissible. The number of diseases is less important than the impact transfusion-transmissible disease has had on our blood transfusion practices. We have slowly developed a culture of caution regarding the potential of any newly discovered agent to be transmitted by blood.

For example, witness the reaction to the potential risk presented by West Nile virus. Donors were removed from the blood supply chain after the possibility of transfusion-transmission of this disease was recognized.¹⁹ Significant sums of money were spent on developing a serological test to screen and remove contaminated units. The same is true of the prion and Creutzfeldt-Jakob disease. The blood collection system in the United States will not accept as donors anyone who has spent more than 6 months in the United Kingdom in recent years. The end result of this culture of caution is twofold — a reduction in the blood supply and increases in the cost of providing a safe product.

Table 2 Transfusion Reactions: Symptoms, Causes, and Incidence Reaction Symptoms Cause Incidence Febrile non-hemolytic acute transfusion Temperature rise greater than 1° C, chills, rigors, shivering Leukotrienes and cytokines from infused blood 1 in 100 to 1 in 200 transfusions Mild allergic urticarial Urticaria, erythema, cutaneous flushing, hoarseness, stridor Antigen or allergen in transfused blood, donor drug, cytokines, leukotrienes, passive transfer of IgG antibodies, cold Common; 1%-2% Severe allergic anaphylactic Hypotension, tachycardia, loss of consciousness, arrhythmia, shock, cardiac arrest, death IgA in transfused blood given to patient with IgA deficiency Rare Acute hemolytic Hemolysis, fever, chills, nausea, vomiting, pain, dyspnea, tachycardia, hypotension, unexplained intraoperative bleeding, hemoglobinuria, death ABO incompatible blood, or IL-1, IL-6, IL-8, TNF infusions Rare; estimated 1 in 33,000 transfusions. Fatalities estimated 1 in 600,000 units. SAnGUIS study estimate – 0.8% of surgical patients transfused Delayed hemolytic Hemolysis at least 24 hours post-transfusion and up to 6 weeks Donor antibodies to recipient red blood cells 2.9% of transfused patients, more common in multiply transfused patients (eg, sickle cell) Bacterial contamination Fever, chills, nausea, vomiting, shock, death Bacterial contamination of unit during collection with overgrowth during storage. Yersinia enterocolitica and Pseudomonas family most common organisms Unknown Post-transfusion purpura Thrombocytopenia, bleeding, purpura from 5 to 10 days post-transfusion up to 3 weeks Patient’s alloantibody against antigen in transfused blood that reacts with platelets Unknown Hypotensive Hypotension in absence of other symptoms Release of bradykinin through coagulation pathway activation from platelet transfusion Unknown; associated with platelet and plasma transfusion; increased incidence in patients on angiotensin converting enzyme inhibitor drugs Nonimmune hemolysis Acute or delayed mild hemolysis, hemoglobinuria Improper storage or handling of blood Rare Circulatory overload Acute pulmonary edema Iatrogenic volume overload Unknown Hypothermia Aggravation of hypothermia, hemolysis with circulating cold agglutinins Iatrogenic administration of cold blood Common in massive transfusion and trauma if blood warmer not used Hyperkalemia Cardiac arrhythmias Iatrogenic transfusion of old, stored blood Rare; seen in massive transfusion and trauma in renal failure patients and children Acidosis Shock, cardiac arrhythmias Iatrogenic transfusion of old, stored blood Rare; seen in massive transfusion Transfusion-related acute lung injury Acute noncardiogenic pulmonary edema within hours of transfusion, dyspnea, fever, hypoxemia Antibodies in transfused plasma against human leukocyte antigens or granulocyte antigens mediated by lipid inflammatory agents Unknown; probably misdiagnosed and under-reported

Transfusion-Related Immunomodulation

Allogeneic blood produces an immunomodulatory effect. Allogeneic transfusion shifts the immune response to a Th-2 type with secretion of IL-4, IL-5, IL-6, and IL-10 and away from a Th-1 response (IL-2, INF-g, and lymphtoxin). The pro-inflammatory, cell-mediated immune response decreases and the humoral immune response upregulates with resultant antibody production.²⁰ The clinical impact has been shown primarily in two areas — decreased survival and shortened disease-free intervals in patients with cancer and an increased rate of infections in other patients.²¹ The estimated risk of producing immunosuppression from a transfusion of an allogeneic blood product can be calculated because every unit has potential. However, surgeons do not know which patients will have a clinically significant impact and when this will occur. Transfusion-associated immunomodulation infectious risks may be higher in certain surgical patients (eg, patients undergoing cardiac surgery).²² The potential remains for short- and long-term harm from transfusion-associated immunomodulation.

The suspected cause is the passenger leukocyte or soluble leukocyte products. Concentrations of soluble major human leukocyte antigens class I and soluble Fas-ligand molecules are significantly higher in supernatants of blood components containing elevated numbers of residual donor leukocytes, such as packed red blood cells and random-donor platelets. These molecules inhibit mixed lymphocyte responses and cytotoxic T-cell activity and induce apoptosis in Fas-positive cells.²³

The benefit of leukoreduction is unproven with differing results from several studies.²² Surgeons should be aware of the potential for adverse outcomes from immunosuppression with every unit transfused and the potential ability of leukoreduction to reduce the effect.

Red blood cells are gradually destroyed over time during storage and more rapidly than native cells after transfusion. The result is the release of free hemoglobin into the transfused unit and the circulation. Free hemoglobin is a potent vasoconstrictor that has the potential to reduce blood flow to critical, microcapillary beds, as shown in experimental studies of red-cell derived oxygen carriers.²⁴ The impact of transfused free hemoglobin on oxygen delivery is unknown but should be a cause of concern. Stored blood also accumulates cytokines over time that can lead to the systemic inflammatory response syndrome, which may increase the risk of serious, postoperative infection.^25,26

Several investigators have demonstrated microchimerism following blood transfusion.^27,28 Lee et al²⁷ found persistent X-chromosome leukocytes in female trauma patients up to 1 to 1.5 years after transfusion of male-donor blood. The long-term impact is unknown, but the potential consequences are severe and include systemic sclerosis, primary biliary cirrhosis, Sjögren’s syndrome, polymorphic eruption of pregnancy, myositis, and thyroid disease.²⁷ Disturbing reports of an association between blood transfusion at an early age in 37,934 women and the later development of non-Hodgkin’s lymphoma and chronic lymphocytic leukemia demonstrate the potential long-term risks of transfusion and the need for caution in transfusion practices.²⁰

Table 3 Transfusion-Transmitted Diseases: Agent, Clinical Impact, and Risk Agent Disease or Clinical Impact Risk HIV AIDS 1 in 1,000,00043 1 in 500,00044 1 in 493,00023 HBV Hepatitis 1 in 50,00043 1 in 63,00035 Antibodies found in 32.8% of multitransfused children45 HCV Hepatitis 1 in 50043 1 in 10,00046 1 in 125,00047 1 in 103,00035 Antibodies found in 31.3% of multitransfused children45 HDV Superinfection in hepatitis B patients – may lead to fulminant hepatic failure Antibodies found in 1.6% of multitransfused children45 HEV Hepatitis 2.8% of blood donors positive48 HGV Hepatitis – may increase risk of hepatitis C 9% of transfused cardiac surgery patients seroconverted to antibody positive postoperative49 TTV Hepatitis 28% to 53% of long-term HDV patients seropositive50 81.7% of 120 blood donors positive51 5.3% of blood donors positive50 HTLV-I & II Adult T cell leukemia & lymphoma, Myelopathies, Tropical spastic paresis 1 in 50,00043 1 in 64,00035 CMV Ranges from no disease to lethal pneu-monitis in immunocompromised patients Seroprevalence ranges from 40% to 100%52 Parvo B19 Spontaneous abortions — Plasmodium falciparum Malaria 4.1% of healthy donors in Nigeria18 103 reported cases in U.S. over 40 years53 Trypanosoma cruzi Chagas’ disease 1.3 to 1.9 % of donors in Brazil,54 Mexico,55 and Argentina56 Borrelia burgdorferi Lyme disease Transmission found only in isolated cases57 Treponema pallidum Syphilis Fresh blood greatest risk Prion (CJD) Variant CJD — Toxoplasma gondii Toxoplasmosis in immunocompromised patients 36% antibody positive in 392 plasmapheresis donors58 Epstein-Barr Virus Mononucleosis, lymphomas — Babesia microti Babesiosis 0.17% of 155 multiply transfused patients57 Herpes 6 virus Lymphoma, marker for CMV — Borna disease virus Psychiatric illnesses 1.09% of blood donors antibody positive59 8%-50% of psychiatric patients antibody positive60 Abbreviations: CJD = Creuzfeldt-Jakob disease, CMV = cytomegalovirus, HBV = hepatitis B virus, HCV = hepatitis C virus, HDV = hepatitis D virus, HEV = hepatitis E virus, HGV = hepatitis G virus, HIV = human immuno deficiency virus, HTLV I & II = human lymphotropic virus I & II, TTV = transfusion transmitted virus.

Benefits of Allogeneic Blood Transfusion

Most surgeons assume that blood transfusion is beneficial but little proof exists. Our presumption of benefit is based on wartime experience that has been handed down as part of our surgical heritage. The idea that battlefield transfusions saved lives is incontrovertible. However, the product transfused was fresh, whole blood, which is different from stored, packed red blood cells. Furthermore, the oxygen delivery benefit of blood transfusion in the battlefield is confounded by its impact on restoring acute volume losses. Stored blood gradually loses 2,3-diphosphoglycerate concentration, which increases its oxygen affinity. Enzyme levels are increased by 24 to 48 hours after transfusion, but this time lag may have a significant impact on oxygen delivery and consumption.

Animal models of acute hemodilution examining transfusion of fresh versus stored blood have shown that the latter does not raise oxygen consumption immediately post-transfusion.²⁹ Stored red blood cells also lose flexibility and become rigid and unable to conform to smaller vessels. These storage lesions of high affinity for oxygen with decreased tissue release and red cell rigidity cause shunts in the microcirculation, decreasing tissue oxygen consumption.

This may explain the lack of effect from stored allogeneic red blood cells seen in critical care populations. Giving a red blood cell transfusion to a critically ill patient gives a false sense of security because oxygen delivery calculated from increased hemoglobin makes it appear that more oxygen is being delivered to the tissues then may be the case. The desired benefit from transfusion of increased oxygen consumption during acute tissue ischemia may not be immediately attainable with transfusion of stored allogeneic or autologous blood.

If one relies on the precepts of evidence-based medicine, the absence of proof of the benefit of blood transfusion is striking. No one has ever proven through a randomized, controlled trial that blood transfusion is essential or improves outcome in any group of patients. In fact, the contrary has been shown in several studies of different transfusion triggers in critically ill, intensive care patients.^30,31 A similar, large scale study of transfusion-related outcomes in 8,787 patients with hip fractures showed that a liberal transfusion policy to a peak hemoglobin of 10 gm/dL did not improve either 30- or 90-day survival when compared to a policy of restricting transfusion to a maximum hemoglobin of 8 g/dL.³²

The most obvious arena in which blood seems beneficial if not essential is in the resuscitation of trauma patients or those who have suffered rapid blood loss. It is necessary, however, to separate the volume effect of blood from its oxygen carrying capability while remembering that blood should be used specifically for the latter purpose in resuscitation.³³ The majority of the life-giving effect of blood during resuscitation is derived from its volume, not from an increase in oxygen delivery. Low volume, hypertonic saline resuscitation regimens coupled with a scoop and run approach to trauma have proven to be as effective as traditional, volume resuscitation.³⁴

A growing experience with the Jehovah’s Witness population has shown that patients can survive with acute blood loss and severe anemia without transfusion, dismissing the idea that a certain amount of blood loss requires transfusion.³⁵ Studies in this population have helped in the understanding of the risk stratification better with regard to transfusion need. Carson et al³⁶ showed that nontransfused surgical patients with heart disease are at greater risk of death when hemoglobin falls below 8 g/dL. Data suggest that patients with cardiopulmonary disease may benefit from higher perioperative hemoglobin levels, but no one has proven that red cell transfusion will reverse mortality.

Risks and Benefits of Autologous Alternatives

The risks associated with the use of autologous blood depend in part on the alternative used. Stored, predonated autologous blood carries the same risk for ABO incompatibility, bacterial overgrowth, and storage lesions as allogeneic blood. The process of predonation carries some risk of adverse reactions.³⁷ An increased incidence of reactions is associated with donor age under 17 years, weight more than 110 lbs, female gender, and a history of previous reactions. Predonation produces preoperative anemia that may lead to increased overall transfusion rates of both allogeneic and autologous blood.^38,39

Acute normovolemic hemodilution eliminates the risks of bacterial overgrowth and storage lesions because the blood is returned to the patient within hours of its removal. ABO incompatibility errors do not occur because the blood does not leave the patient. Concerns exist over the limits of hemodilution and its safety at low hemoglobins. When handled correctly by an experienced anesthesiologist, acute normovolemic hemodilution is safe and effective. Acute normovolemic hemodilution also provides the additional benefits of improved tissue oxygenation and microcirculatory flow from decreased viscosity and loss of fewer red cells per unit volume from bleeding.

Autotransfusion of salvaged blood eliminates the oxygen delivery lesions and incompatibility reactions associated with stored blood. However, reinfusion of shed blood has its own, unique set of complications. The use of unwashed or unprocessed blood reinfused through a filter exposes the patient to the risks of hemogobinuria and renal damage as well as reactions from activated clotting factors, cytokines, and other vasoactive substances.⁴⁰ Processing of blood through cell-salvage devices eliminate most of these complications.

The benefits of the three alternatives in terms of reducing reliance on allogeneic blood need and its associated risks are well documented.⁴¹ These alternatives provide the surgeon with fresh red blood cells, which may be the best oxygen carriers available. Decreasing risk and increasing benefit from blood transfusion begins with individualized transfusion prescriptions based on knowledge of risks and benefits, practice patterns, and patient characteristics. Prevention of surgical bleeding and appropriate modification of procedures benefits all patients. Avoidance of allogeneic blood whenever possible eliminates attendant risks. When allogeneic blood is necessary, transfusing one unit at a time and assessing benefit based on clinically defined goals such as improvement in respiratory function is a sound practice. Risks for an individual patient are cumulative depending on the number of units of blood and blood products given. The goal is not to gamble with patients’ lives but to assure that benefit outweighs risk as much as possible.

The absolute hemoglobin transfusion trigger remains an elusive goal. Absolute hemoglobin transfusion medicine may not exist except in a relative sense. The transfusion trigger has declined from 10 g/dL in the 1940s to 7 g/dL-8 g/dLs at present. A recently published analysis of survival in nontransfused surgical patients with low hemoglobin levels showed that mortality increase as hemoglobin drops.⁴² However, the fact that some of these patients survived with hemoglobins below 3 g/dL (the accepted physiologic limit of red cell mass needed for oxygen delivery) suggests that there is more to survival than blood alone. Surgeons should focus attention on clinical indications for transfusion and on all the variables that affect outcome in anemic patients.

Blood Management and the Orthopedic Patient

Thorough preoperative planning is essential to reducing or avoiding perioperative allogeneic transfusion. Several investigators have documented the value of an overall coordinated approach to blood management in orthopedic surgery. Slappendel et al⁴³ used information derived from a database of 28,861 orthopedic surgery patients to develop an algorithm for reduction of blood transfusion. Important steps included enforcement of predefined transfusion triggers, use of cyclooxygenase-2-selective and nonsteroidal anti-inflammatory drugs only in the perioperative period, erythropoietin and iron therapy, cell salvage during and after surgery, and selective use of aprotinin. The algorithm led to an 80% reduction in transfusion rates with the added benefit of a 40% reduction in deep wound infections. Graham et al⁴⁴ had a similar success in a group of Canadian hospitals. Reports of successful joint replacement without blood transfusion emphasize the value of such approaches.⁴⁵

Presurgical assessment and planning must include recognition of pre-existing anemia and introduction of therapy to correct before surgery. The use of recombinant human erythropoietin or iron therapy has been effective for this purpose.^46-48 Erythropoietin acts an accelerant of red blood cell production by increasing both the number and rate of maturation of colony-forming erythroblasts. Iron is incorporated into the pro-erythrocyte later in its maturation cycle. Iron, whether given orally or intravenously, stimulates reticulocytosis but at a slower than desirable rate for preoperative surgical candidates. Erythropoietin increases red cell mass, but the new cells are hypochromic and microcytic because they lack iron.⁴⁹ Therefore, it is important to treat patients with iron and erythropoietin to correct anemia before surgery. Erythropoietin and iron therapy increases the volume of blood collected using pre-donation strategies.

Use of Autologous Blood

Many orthopedic surgeons have used preoperative autologous donation with success. However, preoperative autologous donation carries the risk of stored blood, inconvenience to the patient, increased costs when compared to allogeneic blood, and high wastage. Approximately 50% of patients who donate blood before surgery are anemic on the day of surgery and receive additional allogeneic transfusions. For every two units donated, on average, one unit gets transfused.^50-52 More cost-effective autologous blood procurement strategies, such as acute normovolemic hemodilution and red blood cell recovery and reinfusion, are preferable to preoperative autologous donation.

Acute normovolemic hemodilution is a low-cost and effective blood conservation technique that can reduce loss of red cell mass in surgical cases with a high-expected blood loss.^53,54 During acute normovolemic hemodilution, several units of blood are collected from a patient immediately before or after the induction of anesthesia and replaced with either a crystalloid or colloid solution or both. Although bleeding during surgery remains essentially unchanged, blood lost during the surgical procedure contains fewer red cells and clotting factors because the patient’s blood has been diluted. At the conclusion of surgery or when a predetermined transfusion trigger is reached, collected blood may be returned to the patient.

Acute normovolemic hemodilution offers several practical advantages over preoperative autologous donation. Minimal preoperative preparation and negligible patient inconvenience make acute normovolemic hemodilution suitable for both urgent and elective procedures. Moreover, acute normovolemic hemodilution units are collected and stored at room temperature at the patient’s bedside, thus reducing the administrative costs associated with collection, storage, and testing of preoperative autologous donation units as well as the risk of human error.⁵⁴

Autologous blood cell salvage (intraoperative autotransfusion) involves recovery of the patient’s shed blood from a surgical wound, washing or filtering, and reinfusion of the blood into the patient. Reinfusion can be performed continuously during surgery. Autotransfusion is an effective blood conservation option for surgical procedures characterized by massive blood loss or where religious objections exclude the use of allogeneic blood. Technological advances have increased system automation. Furthermore, newer devices can process small blood volumes (30 mL or less), require low priming volumes, and offer higher processing speed and better end product quality.

Postoperative cell recovery devices have been used successfully in total knee replacement surgery, in which the majority of blood loss occurs after the wound is closed and the tourniquet is released.^55-57 This remains an effective alternative as long as blood is collected for only 6 hours after surgery.

The essential element of reducing transfusion need in surgical patients is to prevent blood loss. Surgeons are trained in the art of gentle tissue handling, recognition and avoidance of potential bleeding sources, and rapid control of unexpected hemorrhage to accomplish this goal. Traditionally, this has been accomplished with electrocautery, using either monopolar or bipolar instruments.^58-62 Newer modifications to electrocautery include the use of an argon beam–enhanced device that produces a stream of argon gas around the cautery tip that coagulates vessels up to 3 mm in diameter while minimizing tissue trauma.¹⁵ The TissueLink device (Tissuelink, Dover, New Hampshire), which combines a conductive fluid infused at the point of tissue contact with radiofrequency energy to seal tissue, has been used in general surgery and is extending into the orthopedic arena.⁵⁹

Coagulation is a complex process that requires the interaction of both cellular and circulating blood elements. Research into the action of these components combined with the ability to purify and concentrate proteins has led to the creation of tissue, or fibrin, sealants. These products are combinations of purified thrombin and fibrinogen from either bovine or animal sources that reproduce the last states of the coagulation cascade, that is, the conversion of fibrinogen into fibrin monomers and the cross-linking of these into an insoluble fibrin matrix.⁶² The sealants typically are provided in two syringes, the first containing concentrated fibrinogen and aprotinin, the second containing thrombin and CaCl2 in equal parts. A variety of mixing tips are available to permit pinpoint or spray application to a cut or bleeding surface. These products have been shown to reduce both blood loss and transfusion need in surgical procedures. Pharmacological and mechanical blood conservation procedures are valuable adjuncts but cannot replace rigorous hemostasis and good surgical technique. For operative procedures with a high expected blood loss, staged surgery may be part of an overall blood conservation strategy.

Although the alternatives can be used individually with success, they are most effective when used together in a blood management strategy that is individualized to a specific patient. For example, a patient scheduled for an elective joint replacement surgery that typically leads to a two-unit red cell transfusion should be assessed for anemia or iron deficiency several weeks before surgery. If present, these can be corrected with the use of iron and erythropoietin therapy to increase hematocrit, thereby improving a patient’s tolerance to anticipated blood loss. The use of acute normovolemic hemodilution can reduce the number of shed red cells per unit volume, thus decreasing red blood cell volume lost. Shed blood can be collected and reinfused within the first 6 hours after surgery.

Conclusion

A number of safe and cost-effective therapeutic options are available for the potential management of all patients without allogeneic blood transfusion. Orthopedic surgeons should consider blood management using these options for all patients to provide them with safe and effective therapy, while minimizing the risks of allogeneic blood and preserving our decreasing blood resources.

References

1. Sugarman J, Harland R. Acute yet non-emergent patients. In: Surgical Ethics. New York, NY: Oxford University Press; 1998:116-132.
2. Williamson L, Cohen H, Love E, Jones H, Todd A, Soldan K. The Serious Hazards of Transfusion (SHOT) initiative: the UK approach to haemovigilance. Vox Sang. 2000; 78:291-295.
3. Silliman CC. Transfusion-related acute lung injury. Transfus Med Rev. 1999; 13:177-186.
4. Linden J, Pau B, Dressler K. A report of 104 transfusion errors in New York State. Transfusion. 1992; 32:601-606.
5. Linden JV. Errors in transfusion medicine: scope of the problem. Arch Pathol Lab Med. 1999; 123:563-565.
6. Mercuriali F. Bedside transfusion errors: analysis of 2 years’ use of a system to monitor and prevent transfusion errors. Vox Sang. 1996; 70:16-20.
7. McManigal S, Sims KL. Intravascular hemolysis secondary to ABO incompatible platelet products: an underrecognized transfusion reaction. Am J Clin Pathol. 1999; 111:202-206.
8. Davenport R. Management of transfusion reactions. In: Transfusion Therapy: Clinical Principles and Practice. Bethesda, MD: AABB Press; 1999:359-378.
9. Bluemle LJ. Hemolytic transfusion reactions causing acute renal failure: serologic and clinical considerations. Postgrad Med. 1965; 30:583-590.
10. Sazama K. Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion. 1990; 30:583-588.
11. Haverly RM, Harrison CR, Dougherty TH. Yersinia enterocolitica bacteremia associated with red blood cell transfusion. Arch Pathol Lab Med. 1996; 120:499-500.
12. Burstain JM. Rapid identification of bacterially contaminated platelets using reagent strips: glucose and pH analysis as markers of bacterial metabolism. Transfusion. 1997; 37:255-258.
13. Haditsch M. Yersinia enterocolitica septicemia in autologous blood transfusion. Transfusion. 1994; 10:907-909.
14. Dry SM. The pathology of transfusion-related acute lung injury. Am J Clin Pathol. 1999; 112:216-221.
15. Densmore TL. Prevalence of HLA sensitization in female apheresis donors. Transfusion. 1999; 39:103-106.
16. Silliman CC, Boshkov LK, Mehdizadehkashi Z, et al. Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors. Blood. 2003; 101:454-462.
17. Webert KE, Blajchman MA. Transfusion-related acute lung injury. Transfus Med Rev. 2003; 17:252-262.
18. Blajchman MA. Immunomodulation and blood transfusion. Am J Ther. 2002; 9:389-395.
19. Update: Detection of West Nile virus in blood donations-United States, 2003. Morb Mortal Wkly Rep. 2003; 2:916-919.
20. Cerhan JR, Wallace RB, Dick F, et al. Blood transfusions and risk of non-Hodgkin's lymphoma subtypes and chronic lymphocytic leukemia. Cancer Epidemiol Biomarkers Prev. 2001; 10:361-368.
21. Vamvakas EC. WBC-containing allogeneic blood transfusion and mortality: a meta-analysis of randomized controlled trials. Transfusion. 2003; 43:963-973.
22. Ghio M, Contini P, Mazzei C, et al. Soluble HLA class I and Fas ligand molecules in blood components and their role in the immunomodulatory effects of blood transfusions. Leuk Lymphoma. 2000; 39:29-36.
23. Creteur J, Vincent JL. Hemoglobin solutions. Crit Care Med. 2003; 31:S698-S707.
24. Shander A. Emerging risks and outcomes of blood transfusion in surgery. Semin Hematol. 2004; 41:117-124.
25. Taylor RW, Manganaro L, O'Brien J, Trottier SJ, Parkar N, Veremakis C. Impact of allogenic packed red blood cell transfusion on nosocomial infection rates in the critically ill patient. Crit Care Med. 2002; 30:2249-5224.
26. Nelson JL. Microchimerism in human health and disease. Autoimmunity. 2003; 36:5-9.
27. Lee TH, Paglieroni T, Ohto H, Holland PV, Busch MP. Survival of donor leukocyte subpopulations in immunocompetent transfusion recipients: frequent long-term microchimerism in severe trauma patients. Blood. 1999; 93:3127-3139.
28. Marik PE, Sibbald WJ. Effect of stored-blood transfusion on oxygen delivery in patients with sepsis. JAMA. 1993; 269:3024-3029.
29. Hebert PC. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care: transfusion requirements in critical care investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999; 340:409-417.
30. Corwin HL, Parsonnet KC, Gettinger A. RBC transfusion in the ICU. Is there a reason? Chest. 1995; 108:767-771.
31. Carson JL. Perioperative blood transfusion and postoperative mortality. JAMA. 1998; 279:199-205.
32. Shoemaker WC, Wo CC. Circulatory effects of whole blood, packed red cells, albumin, starch, and crystalloids in resuscitation of shock and acute critical illness. Vox Sang. 1998; 74:69-74.
33. Bickell WH. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med. 1994; 331:1105-1109.
34. Spence RK. Transfusion and surgery. Curr Probl Surg. 1993; 30:1101-1180.
35. Wittmann PH, Wittmann FW. Total hip replacement surgery without blood transfusion in Jehovah's Witnesses. Br J Anaesth. 1992; 68:306-307.
36. Carson JL. Effect of anaemia and cardiovascular disease on surgical mortality and morbidity. Lancet. 1996; 348:1055-1060.
37. Spiess B. Autologous blood donation: hemodynamics in a high-risk patient population. Transfusion. 1992; 32:17-22.
38. Goodnough LT. Transfusion medicine. First of two parts-blood transfusion. N Engl J Med. 1999; 340:438-447.
39. Goodnough LT, Verbrugge D, Marcus RE. The relationship between hematocrit, blood lost, and blood transfused in total knee replacement: implications for postoperative blood salvage and reinfusion. Am J Knee Surg. 1995; 8:83-87.
40. Dzik W. Blood salvage: washed versus nonwashed. In: Autotransfusion: Therapeutic Principles and Trends. Detroit, MI: Gregory Appleton; 1997:319-328.
41. Spence RK. Surgical red blood cell transfusion practice policies. Am J Surg. 1995; 170:3S-15S.
42. Carson JL, Noveck H, Berlin JA, Gould SA. Mortality and morbidity in patients with very low postoperative Hb levels who receive blood transfusion. Transfusion. 2002; 42:812-818.
43. Slappendel R, Dirksen R, Weber EW, van der Schaaf DB. An algorithm to reduce allogenic red blood cell transfusions for major orthopedic surgery. Acta Orthop Scand. 2003; 74:569-575.
44. Graham ID, Alvarez G, Tetroe J, McAuley L, Laupacis A. Factors influencing the adoption of blood alternatives to minimize allogeneic transfusion: the perspective of eight Ontario hospitals. Can J Surg. 2002; 45:132-140.
45. Keating EM, Meding JB. Perioperative blood management practices in elective orthopaedic surgery. Am Acad Orthop Surg. 2002; 10:393-400.
46. Earnshaw P. Blood conservation in orthopaedic surgery: the role of epoetin alfa. Int Orthop. 2001; 25:273-278.
47. Lofthouse RA, Boitano MA, Davis JR, Jinnah RH. Preoperative administration of epoetin alfa to reduce transfusion requirements in elderly patients having primary total hip or knee reconstruction. J South Orthop Assoc. 2000; 9:175-181.
48. Henry DH, Bowers P, Romano MT, Provenzano R. Epoetin alfa: clinical evolution of a pleiotropic cytokine. Arch Intern Med. 2004; 164:262-276.
49. Goodnough LT, Price TH, Rudnick S, Soegiarso RW. Preoperative red blood cell production in patients undergoing aggressive autologous blood phlebotomy with and without erythropoietin therapy. Transfusion. 1992; 32:441-445.
50. Goldman M, Savard R, Long A, Gelinas S, Germain M. Declining value of preoperative autologous donation. Transfusion. 2002; 42:819-823.
51. Forgie M, Wells P, Laupacis A, Fergusson D. Preoperative autologous donation decreases allogeneic transfusion but increases exposure to all red cell transfusion: results of a meta analysis. International Study of Perioperative Transfusion (ISPOT) Investigators. Arch Intern Med. 1998; 158:610-616.
52. Schmied H, Schiferer A, Sessler DI, Meznik C. The effects of red-cell scavenging, hemodilution, and active warming on allogenic blood requirements in patients undergoing hip or knee arthroplasty. Anesth Analg. 1998; 86:387-391.
53. Goodnough LT, Monk TG, Brecher ME. Acute normovolemic hemodilution should replace the preoperative donation of autologous blood as a method of autologous-blood procurement. Transfusion. 1998; 38:473-476.
54. Warner C. The use of the orthopaedic perioperative autotransfusion (OrthoPAT) system in total joint replacement surgery. Orthop Nurs. 2001; 20:29-32.
55. Huet C, Salmi LR, Fergusson D, et al. A meta-analysis of the effectiveness of cell salvage to minimize perioperative allogeneic blood transfusion in cardiac and orthopedic surgery. International Study of Perioperative Transfusion (ISPOT) Investigators. Anesth Analg. 1999; 89:861-869.
56. Benli IT, Akalin S, Duman E, Citak M, Kis M. The results of intraoperative autotransfusion in orthopaedic surgery. Bull Hosp Jt Dis. 1999; 58:184-187.
57. Goodnough LT, Shander A, Spence R. Bloodless medicine: clinical care without allogeneic blood transfusion. Transfusion. 2003; 43:668-676.
58. Velanovich V, Weaver M. Partial splenectomy using a coupled saline-radiofrequency hemostatic device. Am J Surg. 2003; 1:185.
59. Braswell C, Campos J, Spence RK. Reducing operative blood loss during hepatic surgery: from the middle ages to the space age. Current Surgery. 2001; 58:472-477.
60. Fasulo F. Cavitron Ultrasonic Surgical Aspirator (CUSA) in liver resection. Int Surg. 1992; 77:64-66.
61. Une Y. Water jet scalpel for liver resection in hepatocellular carcinoma with or without cirrhosis. Int Surg. 1996; 81:45-48.
62. Wang GJ, Hungerford DS, Savory CG, et al. Use of fibrin sealant to reduce bloody drainage and hemoglobin loss after total knee arthroplasty: a brief note on a randomized prospective trial. J Bone Joint Surg Am. 2001; 83:1503-1505.